Identifying dependability requirements for space software systems

Computer systems are increasingly used in space, whether in launch vehicles, satellites, ground support and payload systems. Software applications used in these systems have become more complex, mainly due to the high number of features to be met, thus contributing to a greater probability of hazards related to software faults. Therefore, it is fundamental that the specification activity of requirements have a decisive role in the effort of obtaining systems with high quality and safety standards. In critical systems like the embedded software of the Brazilian Satellite Launcher, ambiguity, non-completeness, and lack of good requirements can cause serious accidents with economic, material and human losses. One way to assure quality with safety, reliability and other dependability attributes may be the use of safety analysis techniques during the initial phases of the project in order to identify the most adequate dependability requirements to minimize possible fault or failure occurrences during the subsequent phases. This paper presents a structured software dependability requirements analysis process that uses system software requirement specifications and traditional safety analysis techniques. The main goal of the process is to help to identify a set of essential software dependability requirements which can be added to the software requirement previously specified for the system. The final results are more complete, consistent, and reliable specifications

Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis

Objectives: To investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA). Methods: Patients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high). Results: In TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (<0.1 μg/ml) at 3 and 6 mg/kg but were greater than 2 μg/ml at 10 mg/kg, whereas the levels were approximately 1 μg/ml for each dosage group in TNF-low patients. Conclusion: In patients with RA, baseline-TNF is significantly associated with the clinical response to infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab

Serum and urinary ferritin levels in patients with rheumatoid arthritis

The serum and urinary ferritin levels in 52 RA patients were measured by the 2-site immunoradiometric assay method. Serum ferritin levels in RA patients correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) but not with serum iron levels and hemoglobin concentrations, although they were within the normal range. High serum ferritin levels were associated with sera with hyper gamma-globulin and rheumatoid factors. In sequential studies, serum ferritin changed in parallel with ESR, CRP and disease activity in a majority of the patients. The urinary ferritin levels and u/s ratios in some RA patients were higher than control values. Higher values were found particularly in the group of patients under gold therapy but not in groups under other treatments.</p

Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice

Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic β-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic β-cells.Masato Yano, Ken Watanabe, Tadashi Yamamoto, Kazutaka Ikeda, Takafumi Senokuchi, Meihong Lu, Tsuyoshi Kadomatsu, Hiroto Tsukano, Masahito Ikawa, Masaru Okabe, Shohei Yamaoka, Toshiro Okazaki, Hisanori Umehara, Tomomi Gotoh, Wen-Jie Song, Koichi Node, Ryo Taguchi, Kazuya Yamagata, Yuichi Oike, Mitochondrial Dysfunction and Increased Reactive Oxygen Species Impair Insulin Secretion in Sphingomyelin Synthase 1-null Mice, Journal of Biological Chemistry, Volume 286, Issue 5, 2011, Pages 3992-4002, ISSN 0021-9258, https://doi.org/10.1074/jbc.M110.179176

Transoral surgery for superficial head and neck cancer: National Multi‐Center Survey in Japan

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1–113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment

Safety and efficacy of infliximab in the treatment of refractory uveoretinitis in Behcet's disease: a large-scale, long-term postmarketing surveillance in Japan

BackgroundInfliximab, an anti-tumor necrosis factor-alpha antibody, has been reported to have excellent efficacy for refractory uveoretinitis in Behcet's disease (RUBD), and was approved for this indication in Japan. However, the long-term safety profile and efficacy in real-world clinical settings in patients with RUBD have not been fully clarified. The BRIGHT study, a prospective, large-scale, long-term postmarketing surveillance (PMS) study, was conducted to investigate the long-term safety and efficacy of infliximab in Japanese patients with RUBD.MethodsAll patients with RUBD who started infliximab treatment between January 2007 and January 2010 were enrolled. Safety was evaluated every 6months for up to 24months after initiation of therapy in 656 patients, and efficacy was evaluated in 650 patients. Patient characteristics were compared using the chi-square or Fisher's exact test. The frequency of ocular attacks before and after infliximab treatment was compared using the Wilcoxon signed-rank test. Independent associated factors for safety or efficacy were identified using multiple logistic regression analysis. A two-sided pvalue <0.05 was considered significant.ResultsAmong the 656 patients evaluated for safety, 555 (84.6%) completed the 24-month study period. The incidence of adverse drug reactions (ADRs) and serious ADRs were 32.32% and 6.10%, respectively, and the safety profile was comparable to that of Japanese PMS of infliximab for other diseases. The most common ADRs and serious ADRs were infections (11.89% and 3.66%). Tuberculosis was reported in two patients, and Pneumocystis jirovecii in one. Identified independent associated factors for infections were comorbid respiratory disease, history of allergic disease, and concomitant use of glucocorticoids. Although infusion reactions were observed in 11.13% of patients, most were non-serious. The response rate at 24months by physician global assessment was 80.7%. Median frequency of ocular attacks per 6months significantly decreased compared with that before infliximab treatment (2.0 to 0.0), and corrected visual acuity was maintained during the study.ConclusionsInfliximab treatment had good tolerability and efficacy in Japanese patients with RUBD in this large-scale, long-term PMS. Infliximab treatment seemed to be a good treatment option for RUBD in real-world clinical settings.Trial registrationUMIN Clinical Trials Registry, UMIN000027733. Retrospectively registered on 6 June 2017